Safety and Effectiveness of Short-Term Anti-HIV Drug Therapy for Recent HIV-1 Infection

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ClinicalTrials.gov Identifier: NCT00414518

Recruitment Status : Completed

First Posted : December 21, 2006

Results First Posted : February 20, 2013

Last Update Posted : February 20, 2013

Sponsor:

Collaborator:

National Institute of Allergy and Infectious Diseases (NIAID)

Information provided by (Responsible Party):

University of Colorado, Denver

Study Description

Brief Summary:

The purpose of this study is to determine the safety and effectiveness of an anti-HIV drug regimen followed by treatment interruption in people recently infected with HIV. This study will also compare the effects of a treatment regimen including treatment interruption with a treatment plan based on clinical indicators.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: Tenofovir disoproxil fumarate/Emtricitabine Drug: Lopinavir/Ritonavir	Not Applicable

Detailed Description:

About 6 months after infection, HIV viral load reaches a temporarily stable level known as virus set point. Virus set point is different for each patient and can be a predictor for disease progression. Preliminary studies indicate that early, short-term antiretroviral therapy (ART) given to people newly infected with HIV may lead to lower virus set points and preserved CD4 counts. However, the length of short-term treatment needed to balance the possible adverse effects of ART with the achievement of lower virus set point is not yet known. By lowering the virus set point and maintaining CD4 counts, the need for long-term ART may be postponed. The purpose of this study is to determine the safety and efficacy of a short course of ART on producing a lower virus set point in adults recently infected with HIV.

This study will last at least 28 weeks. Participants will be randomly assigned to one of two arms. Arm A will receive ART for 12 weeks as emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) daily and lopinavir/ritonavir (LPV/RTV) in tablet form twice daily. After 12 weeks, treatment will be interrupted unless the CD4 count is measured to be less than 350 cells/mm^3 on two consecutive occasions during treatment interruption. If that occurs therapy will be resumed. Participants in Arm B will receive no treatment until cluster of differentiation 4 (CD4) counts drop below 350 cells/mm^3, indicating ART is needed. Study visits will occur at study entry, at Weeks 2 and 4, and every 4 weeks thereafter. At each study visit, a physical exam, blood collection, and completion of an adherence questionnaire will occur. Participants are encouraged to enroll in a related substudy that will evaluate HIV viral load in genital secretions.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	16 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	An Open-Label Randomized Clinical Trial to Evaluate the Efficacy and Safety of Short Course Antiretroviral Therapy for Acute or Recent HIV-1 Infection in Zimbabwe and the United States
Study Start Date :	January 2007
Actual Primary Completion Date :	February 2010
Actual Study Completion Date :	February 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Emtricitabine Tenofovir Ritonavir Lopinavir Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment interruption Oral Tenofovir disoproxil fumarate/Emtricitabine and Lopinavir/Ritonavir for 12 weeks followed by treatment interruption if CD4 count is 450 mm^3 or higher. When CD4 count is less than 350 mm^3 on two separate, consecutive measurements during treatment interruption, therapy will be resumed.	Drug: Tenofovir disoproxil fumarate/Emtricitabine 300 mg Tenofovir disoproxil fumarate/ 200 mg emtricitabine tablet taken orally once daily Other Name: TDF/FTC Drug: Lopinavir/Ritonavir Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily Other Name: LPV/RTV
Experimental: CD4 T cell guided therapy Anti Retroviral Therapy initiated when AIDS-defining illness occurs or if CD4 count is confirmed at less than 350 mm^3 at two separate, consecutive measurements	Drug: Tenofovir disoproxil fumarate/Emtricitabine 300 mg Tenofovir disoproxil fumarate/ 200 mg emtricitabine tablet taken orally once daily Other Name: TDF/FTC Drug: Lopinavir/Ritonavir Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily Other Name: LPV/RTV

Outcome Measures

Primary Outcome Measures :

Plasma HIV-1 Viral Load (Copies/ml) at Week 24 as Compared Between the Two Arms [ Time Frame: At Week 24 ]
Number of Participants Experiencing Either an AIDS-defining Event, a Grade 3 or 4 Adverse Event, or Acute Retroviral Syndrome [ Time Frame: At Week 24 ]
Viral Set Point [ Time Frame: Throughout study ]
set point is reached after the immune system has developed HIV antibodies and begins to attempt to fight the virus

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Acute or recent HIV-1 infection. More information about this criterion can be found in the protocol.
CD4 count 500 cells/mm3 or greater
No evidence of prior or current AIDS-defining illness
No signs or symptoms of HIV infection or AIDS-defining illness that, in the opinion of the investigator, requires ART
Willing to use acceptable forms of contraception

Exclusion Criteria:

Prior treatment with any antiretroviral drug for more than 7 days
Use of certain drugs within 21 days of study entry
Prior receipt of investigational anti-HIV-1 vaccine
Ongoing therapy with systemic corticosteroids, chemotherapeutic agents, nephrotoxic systemic agents, immunomodulatory treatments, or investigational agents
Known allergy/sensitivity to study drugs or their formulations
Current drug or alcohol use or abuse that, in the opinion of the investigator, may interfere with the study
Serious medical or psychiatric illness that may interfere with the study
Hepatitis B infected
Pregnancy or breastfeeding

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00414518

Locations


United States, Colorado
University of Colorado Health Sciences Center
Denver, Colorado, United States, 80262
United States, Georgia
AIDS Research Consortium of Atlanta
Atlanta, Georgia, United States, 30308
Zimbabwe
University of Zimbabwe College of Health Sciences
Harare, Zimbabwe

Sponsors and Collaborators

University of Colorado, Denver

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Study Chair:	Michelle A. Barron, MD	Division of Infectious Disease, University of Colorado Health Sciences Center
Study Chair:	Margaret Borok, MRCP	Department of Medicine, University of Zimbabwe

More Information

Publications:

Altfeld M, Rosenberg ES, Shankarappa R, Mukherjee JS, Hecht FM, Eldridge RL, Addo MM, Poon SH, Phillips MN, Robbins GK, Sax PE, Boswell S, Kahn JO, Brander C, Goulder PJ, Levy JA, Mullins JI, Walker BD. Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J Exp Med. 2001 Jan 15;193(2):169-80.

Fidler S, Oxenius A, Brady M, Clarke J, Cropley I, Babiker A, Zhang HT, Price D, Phillips R, Weber J. Virological and immunological effects of short-course antiretroviral therapy in primary HIV infection. AIDS. 2002 Oct 18;16(15):2049-54.

Coombs RW, Speck CE, Hughes JP, Lee W, Sampoleo R, Ross SO, Dragavon J, Peterson G, Hooton TM, Collier AC, Corey L, Koutsky L, Krieger JN. Association between culturable human immunodeficiency virus type 1 (HIV-1) in semen and HIV-1 RNA levels in semen and blood: evidence for compartmentalization of HIV-1 between semen and blood. J Infect Dis. 1998 Feb;177(2):320-30.

Gallant JE. Current status of antiretroviral treatment interruption and intermittent therapy strategies. MedGenMed. 2002 Sep 19;4(3):19. Review.

Gulick RM. Structured treatment interruption in patients infected with HIV: a new approach to therapy. Drugs. 2002;62(2):245-53. Review.


Responsible Party:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT00414518 History of Changes
Obsolete Identifiers:	NCT00525070, NCT01030172
Other Study ID Numbers:	06-0757 P01AI055356 ( U.S. NIH Grant/Contract )
First Posted:	December 21, 2006 Key Record Dates
Results First Posted:	February 20, 2013
Last Update Posted:	February 20, 2013
Last Verified:	January 2013

Keywords provided by University of Colorado, Denver:


Acute Infection Early HIV Infection Short-Term Antiretroviral Therapy	Treatment Interruption Antiretroviral Drug (ARV) ART

Additional relevant MeSH terms:


Infection Communicable Diseases HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Lopinavir Tenofovir	Emtricitabine HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors

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